This invention relates generally to the field of bacterial antigens and their use, for example, as immunogenic agents in humans and animals to stimulate an immune response. More specifically, it relates to the vaccination of mammalian species with a polypeptide comprising at least one conserved histidine triad residue (HxxHxH-SEQ ID NO: 12) and at least one helix-forming polypeptide obtained from Streptococcus pneumoniae as a mechanism for stimulating production of antibodies that protect the vaccine recipient against infection by a wide range of serotypes of pathogenic S. pneumoniae. Further, the invention relates to antibodies against such polypeptides useful in diagnosis and passive immune therapy with respect to diagnosing and treating such pneumococcal infections.
In a particular aspect, the present invention relates to the prevention and treatment of pneumococcal infections such as infections of the middle ear, nasopharynx, lung and bronchial areas, blood, CSF, and the like, that are caused by pneumococcal bacteria.
Streptococcus pneumoniae is a gram positive bacteria which is a major causative agent in invasive infections in animals and humans, such as sepsis, meningitis, otitis media and lobar pneumonia (Tuomanen et al. New Engl. J. Med. 322:1280-1284 (1995)). As part of the infective process, peumococci readily bind to non-inflamed human epithelial cells of the upper and lower respiratory tract by binding to eukaryotic carbohydrates in a lectin-like manner (Cundell et al., Micro. Path. 17:361-374 (1994)). Conversion to invasive pneumococcal infections for bound bacteria may involve the local generation of inflammatory factors which may activate the epithelial cells to change the number and type of receptors on their surface (Cundell et al., Nature, 377:435-438 (1995)). Apparently, one such receptor, platelet activating factor (PAF) is engaged by the pneumococcal bacteria and within a very short period of time (minutes) from the appearance of PAF, pneumococci exhibit strongly enhanced adherence and invasion of tissue. Certain soluble receptor analogs have been shown to prevent the progression of pneumococcal infections (Idanpaan-Heikkila et al., J. Inf. Dis., 176:704-712 (1997)). A number of various other proteins have been suggested as being involved in the pathogenicity of S. pneumoniae. There remains a need for identifying polypeptides having epitopes in common from various strains of S. pneumoniae in order to utilize such polypeptides as vaccines to provide protection against a wide variety of S. pneumoniae. 
In accordance with the present invention, there is provided vaccines and vaccine compositions that include polypeptides obtained from S. pneumoniae and/or variants of said polypeptides and/or active fragments of such polypeptides.
The active fragments, as hereinafter defined, include a histidine triad residue(s) and/or coiled coil regions of such polypeptides.
The term xe2x80x9cpercent identityxe2x80x9d or xe2x80x9cpercent identical,xe2x80x9d when referring to a sequence, means that a sequence is compared to a claimed or described sequence from an alignment of the sequence to be compared (the xe2x80x9cCompared Sequencexe2x80x9d) with the described or claimed sequence (the xe2x80x9cReference Sequencexe2x80x9d). The percent identity is determined as follows:
Percent Identity=[1xe2x88x92(C/R)]100
wherein C is the number of differences between the Reference Sequence and the Compared Sequence over the length of the alignment between the Compared Sequence and the Reference Sequence wherein (i) each base or amino acid in the Reference Sequence that does not have an aligned base or amino acid in the Compared Sequence and (ii) each gap in the Reference Sequence and (iii) each aligned base or amino acid in the Reference Sequence that is different from an aligned base or amino acid in the Compared Sequence, each being a difference; and R is the number of bases or amino acids in the Reference Sequence over the length of the alignment with the Compared Sequence with any gap created in the Reference Sequence also being counted as a base or amino acid.
If an alignment exists between the Compared Sequence and the Reference Sequence in which the Percent Identity as calculated above is about equal to or greater than a specified minimum Percent Identity then the Compared Sequence has the specified minimum Percent Identity to the Reference Sequence even though alignments may exist in which the hereinabove calculated Percent Identity is less than the specified Percent Identity.
xe2x80x9cIsolatedxe2x80x9d in the context of the present invention with respect to polypeptides and/or polynucleotides means that the material is removed from its original environment (e.g., the natural environment if it is naturally occurring). For example, a naturally-occurring polynucleotide or polypeptide present in a living organism is not isolated, but the same polynucleotide or polypeptide, separated from some or all of the co-existing materials in the natural system, is isolated. Such polynucleotides could be part of a vector and/or such polynucleotides or polypeptides could be part of a composition, and still be isolated in that such vector or composition is not part of its natural environment. The polypeptides and polynucleotides of the present invention are preferably provided in an isolated form, and preferably are purified to homogeneity.